Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4771 | 14536;14537;14538 | chr2:178738142;178738141;178738140 | chr2:179602869;179602868;179602867 |
| N2AB | 4454 | 13585;13586;13587 | chr2:178738142;178738141;178738140 | chr2:179602869;179602868;179602867 |
| N2A | 3527 | 10804;10805;10806 | chr2:178738142;178738141;178738140 | chr2:179602869;179602868;179602867 |
| N2B | 4408 | 13447;13448;13449 | chr2:178738142;178738141;178738140 | chr2:179602869;179602868;179602867 |
| Novex-1 | 4533 | 13822;13823;13824 | chr2:178738142;178738141;178738140 | chr2:179602869;179602868;179602867 |
| Novex-2 | 4600 | 14023;14024;14025 | chr2:178738142;178738141;178738140 | chr2:179602869;179602868;179602867 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.273 | N | 0.551 | 0.215 | 0.252681307341 | gnomAD-4.0.0 | 1.59131E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.8583E-06 | 0 | 0 |
| T/I | rs762249414  |
0.183 | 0.864 | N | 0.642 | 0.165 | 0.366848117066 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/I | rs762249414 |
0.183 | 0.864 | N | 0.642 | 0.165 | 0.366848117066 | gnomAD-4.0.0 | 3.18269E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85834E-06 | 0 | 3.02425E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.15 | likely_benign | 0.1735 | benign | -1.302 | Destabilizing | 0.273 | N | 0.551 | neutral | N | 0.42229829 | None | None | N |
| T/C | 0.618 | likely_pathogenic | 0.6696 | pathogenic | -0.733 | Destabilizing | 0.985 | D | 0.641 | neutral | None | None | None | None | N |
| T/D | 0.7712 | likely_pathogenic | 0.799 | pathogenic | -1.204 | Destabilizing | 0.707 | D | 0.554 | neutral | None | None | None | None | N |
| T/E | 0.565 | likely_pathogenic | 0.6455 | pathogenic | -0.975 | Destabilizing | 0.547 | D | 0.553 | neutral | None | None | None | None | N |
| T/F | 0.3915 | ambiguous | 0.475 | ambiguous | -1.028 | Destabilizing | 0.945 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/G | 0.4924 | ambiguous | 0.5311 | ambiguous | -1.72 | Destabilizing | 0.547 | D | 0.575 | neutral | None | None | None | None | N |
| T/H | 0.4388 | ambiguous | 0.4646 | ambiguous | -1.686 | Destabilizing | 0.985 | D | 0.699 | prob.neutral | None | None | None | None | N |
| T/I | 0.251 | likely_benign | 0.331 | benign | -0.188 | Destabilizing | 0.864 | D | 0.642 | neutral | N | 0.421770708 | None | None | N |
| T/K | 0.4807 | ambiguous | 0.5494 | ambiguous | -0.062 | Destabilizing | 0.477 | N | 0.553 | neutral | N | 0.421526091 | None | None | N |
| T/L | 0.1985 | likely_benign | 0.2416 | benign | -0.188 | Destabilizing | 0.707 | D | 0.535 | neutral | None | None | None | None | N |
| T/M | 0.1366 | likely_benign | 0.167 | benign | -0.256 | Destabilizing | 0.995 | D | 0.637 | neutral | None | None | None | None | N |
| T/N | 0.2836 | likely_benign | 0.3314 | benign | -0.791 | Destabilizing | 0.547 | D | 0.515 | neutral | None | None | None | None | N |
| T/P | 0.9017 | likely_pathogenic | 0.9163 | pathogenic | -0.531 | Destabilizing | 0.928 | D | 0.642 | neutral | N | 0.360015175 | None | None | N |
| T/Q | 0.4141 | ambiguous | 0.4497 | ambiguous | -0.552 | Destabilizing | 0.894 | D | 0.64 | neutral | None | None | None | None | N |
| T/R | 0.3653 | ambiguous | 0.4283 | ambiguous | -0.374 | Destabilizing | 0.864 | D | 0.642 | neutral | N | 0.420720092 | None | None | N |
| T/S | 0.1377 | likely_benign | 0.1425 | benign | -1.119 | Destabilizing | 0.002 | N | 0.343 | neutral | N | 0.371758046 | None | None | N |
| T/V | 0.2029 | likely_benign | 0.2609 | benign | -0.531 | Destabilizing | 0.707 | D | 0.509 | neutral | None | None | None | None | N |
| T/W | 0.8046 | likely_pathogenic | 0.8394 | pathogenic | -1.097 | Destabilizing | 0.995 | D | 0.684 | prob.neutral | None | None | None | None | N |
| T/Y | 0.4991 | ambiguous | 0.5437 | ambiguous | -0.714 | Destabilizing | 0.945 | D | 0.717 | prob.delet. | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.